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Metabolomic study of plasma of patients with abdominal aortic aneurysm

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Abstract

Abdominal aortic aneurysm (AAA) is an important health problem, both because of AAA rupture and death and because of increased cardiovascular mortality. Identification of new biomarkers of AAA may suggest novel pathological mechanisms and targets for new medical treatments to slow AAA progression. Metabolic changes in AAA patients were mainly related to carbohydrate and lipid metabolism and many of these changes can be associated with a situation of insulin resistance (which can be related to metabolic syndrome) together with altered amino acid metabolism. For the first time, metabolites that can be associated with differential metabolism by the gut microflora of AAA patients have also been found. Moreover, aminomalonic acid in plasma has been shown to be the metabolite with the biggest difference between patients suffering from large aneurysm (>5 cm) and controls.

In the quest for adequate biomarkers, suitable for diagnosis and/or monitoring the presence and size of abdominal aortic aneurysm, metabolomics opens new possibilities thanks to the non-targetted approach. That permits to evaluate differences without previous biasing hypotheses.

By coupling signals from 1H NMR and GC-MS, it has been possible to find metabolites, quantitatively different in aneurysm patients when compared with controls.

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References

  1. Sakalihasan N, Limet R, Defawe OD (2005) Abdominal aortic aneurysm. Lancet 365(9470):1577–1589

    Article  CAS  Google Scholar 

  2. Baumgartner I, Hirsch AT, Abola MT, Cacoub PP, Poldermans D, Steg PG, Creager MA, Bhatt DL (2008) Cardiovascular risk profile and outcome of patients with abdominal aortic aneurysm in out-patients with atherothrombosis: data from the Reduction of Atherothrombosis for Continued Health (REACH) Registry. J Vasc Surg 48(4):808–814

    Article  Google Scholar 

  3. Norman P, Le M, Pearce C, Jamrozik K (2004) Infrarenal aortic diameter predicts all-cause mortality. Arterioscler Thromb Vasc Biol 24(7):1278–1282

    Article  CAS  Google Scholar 

  4. Lederle FA, Johnson GR, Wilson SE, Ballard DJ, Jordan WD, Blebea J, Littooy FN, Freischlag JA, Bandyk D, Rapp JH, Salam AA (2002) Rupture rate of large abdominal aortic aneurysms in patients refusing or unfit for elective repair. J Am Med Assoc 287(22):2968–2972

    Article  Google Scholar 

  5. Vega de Céniga M, Esteban M, Quintana JM, Barba A, Estallo L, de la Fuente N, Viviens B, Martin-Ventura JL (2009) Search for serum biomarkers associated with abdominal aortic aneurysm growth—a pilot study. Eur J Vasc Endovasc Surg 37(3):297–299

    Article  Google Scholar 

  6. Baxter BT, Terrin MC, Dalman RL (2008) Medical management of small abdominal aortic aneurysms. Circulation 117(14):1883–1889

    Article  Google Scholar 

  7. Urbonavicius S, Urbonaviciene G, Honoré B, Henneberg EW, Vorum H, Lindholt JS (2008) Potential circulating biomarkers for abdominal aortic aneurysm expansion and rupture—a systematic review. Eur J Vasc Endovasc Surg 36(3):273–280, discussion 81–82

    Article  CAS  Google Scholar 

  8. Golledge J, Tsao PS, Dalman RL, Norman PE (2008) Circulating markers of abdominal aortic aneurysm presence and progression. Circulation 118(23):2382–2392

    Article  Google Scholar 

  9. Ciborowski M, Martin-Ventura JL, Meilhac O, Michel JB, Ruperez FJ, Tuñon J, Egido J, Barbas C (2011) Metabolites secreted by human atherothrombotic aneurysms revealed through a metabolomic approach. J Proteome Res 10(3):1374–1382

    Article  CAS  Google Scholar 

  10. Martinez-Pinna R, Ramos-Mozo P, Madrigal-Matute J, Blanco-Colio LM, Lopez JA, Calvo E, Camafeita E, Lindholt JS, Meilhac O, Delbosc S, Michel JB, Vega de Ceniga M, Egido J, Martin-Ventura JL (2011) Identification of peroxiredoxin-1 as a novel biomarker of abdominal aortic aneurysm. Arterioscler Thromb Vasc Biol 31(4):935–943

    Article  CAS  Google Scholar 

  11. Wheelock CE, Wheelock AM, Kawashima S, Diez D, Kanehisa M, van Erk M, Kleeman R, Heggstrom JZ, Goto S (2009) Systems biology approaches and pathway tools for investigating cardiovascular disease. Mol Biosyst 5(6):588–602

    Article  CAS  Google Scholar 

  12. Martinez-Pinna R, Barbas C, Blanco-Colio LM, Tunon J, Ramos-Mozo P, Lopez JA, Meilhac O, Michel JB, Egido J, Martin-Ventura JL (2010) Proteomic and metabolomic profiles in atherothrombotic vascular disease. Curr Atheroscler Rep 12(3):202–208

    Article  CAS  Google Scholar 

  13. Vallejo M, García A, Tuñón J, García-Martínez D, Angulo S, Martin-Ventura J, Blanco-Colio LM, Almeida P, Egido J, Barbas C (2009) Plasma fingerprinting with GC–MS in acute coronary syndrome. Anal Bioanal Chem 394(6):1517–1524

    Article  CAS  Google Scholar 

  14. Teul J, Ruperez FJ, Garcia A, Vaysse J, Balayssac S, Gilard V, Malet-Martino M, Martin-Ventura JL, Blanco-Colio LM, Tunon J, Egido J, Barbas C (2009) Improving Metabolite Knowledge in Stable Atherosclerosis Patients by Association and Correlation of GC–MS and H-1 NMR Fingerprints. J Proteome Res 8(12):5580–5589

    Article  CAS  Google Scholar 

  15. García-Pérez I, Whitfield P, Bartlett A, Angulo S, Legido-Quigley C, Hanna-Brown M, Barbas C (2008) Metabolic fingerprinting of Schistosoma mansoni infection in mice urine with capillary electrophoresis. Electrophoresis 29(15):3201–3206

    Article  Google Scholar 

  16. Nielsen NPV, Carstensen JM, Smedsgaard J (1998) Aligning of single and multiple wavelength chromatographic profiles for chemometric data analysis using correlation optimised warping. J Chromatogr A 805:17–35

    Article  CAS  Google Scholar 

  17. Tomasi G, van den Berg F, Andersson C (2004) Correlation optimized warping and dynamic time warping as preprocessing methods for chromatographic data. J Chemom 18:231–241

    Article  CAS  Google Scholar 

  18. Skov T, van den Berg F, Tomasi G, Bro R (2006) Automated Alignment of Chromatographic Data. J Chemom 20:484–497

    Article  CAS  Google Scholar 

  19. Gorter PM, Olijhoek JK, van der Graaf Y, Algra A, Rabelink TJ, Visseren FLJ (2004) Prevalence of the metabolic syndrome in patients with coronary heart disease, cerebrovascular disease, peripheral arterial disease or abdominal aortic aneurysm. Atherosclerosis 173(2):363–369

    Article  CAS  Google Scholar 

  20. Olijhoek JK, van der Graaf Y, Banga JD, Algra A, Rabelink TJ, Visseren FLJ (2004) The Metabolic Syndrome is associated with advanced vascular damage in patients with coronary heart disease, stroke, peripheral arterial disease or abdominal aortic aneurysm. Eur Heart J 25(4):342–348

    Article  Google Scholar 

  21. van Kuijk JP, Flu WJ, Chonchol M, Bax JJ, Verhagen HJM, Poldermans D (2010) Metabolic syndrome is an independent predictor of cardiovascular events in high-risk patients with occlusive and aneurysmatic peripheral arterial disease. Atherosclerosis 210(2):596–601

    Article  Google Scholar 

  22. Landaas S (1975) The formation of 2-hydroxybutyric acid in experimental animals. Clin Chim Acta 58(1):23–32

    Article  CAS  Google Scholar 

  23. Gall W, Beebe K, Lawton K, Adam K, Mitchell M, Nakhle P, Ryals JA, Milburn MV, Nannipieri M, Camastra S, Natali A, Ferrannini E, RISC Study Group (2010) alpha-hydroxybutyrate is an early biomarker of insulin resistance and glucose intolerance in a nondiabetic population. PLoS One 5(5):e10883. doi:10.1371/journal.pone.0010883

    Article  Google Scholar 

  24. Gacko M, Ostapowicz R, Chrostek L, Worowska A, Kordecki K (2005) Activity of enzymes with different subcellular localization in the blood plasma of patients with aortic aneurysm. Med Sci Monit 11(4):CR211–CR213

    Google Scholar 

  25. Suhre K, Meisinger C, Doring A, Altmaier E, Belcredi P, Gieger C, Chang D, Milburn MV, Gall WE, Weinberger KM, Mewes HW, Hrabé de Angelis M, Wichmann HE, Kronenberg F, Adamski J, Illig T (2010) Metabolic footprint of diabetes: a multiplatform metabolomics study in an epidemiological setting. PLoS One 5(11):11

    Article  Google Scholar 

  26. Calvani R, Miccheli A, Capuani G, Miccheli AT, Puccetti C, Delfini M, Iaconelli A, Nanni G, Mingrone G (2010) Gut microbiome-derived metabolites characterize a peculiar obese urinary metabotype. Int J Obes 34(6):1095–1098

    Article  CAS  Google Scholar 

  27. Van Buskirk JJ, Kirsch WM, Kleyer DL, Barkley RM, Koch TH (1984) Aminomalonic acid: identification in Escherichia coli and atherosclerotic plaque. Proc Natl Acad Sci U S A 81(3):722–725

    Article  Google Scholar 

  28. Chakrabarti M, Cheng KT, Spicer KM, Kirsch WM, Fowler SD, Kelln W, Griende S, Nehlsen-Cannarella S, Willerson R, Spicer SS, Koch T (1995) Biodistribution and radioimmunopharmacokinetics of 131I-Ama monoclonal antibody in atherosclerotic rabbits. Nucl Med Biol 22(6):693–697

    Article  CAS  Google Scholar 

  29. Dean RT, Fu S, Stocker R, Davies MJ (1997) Biochemistry and pathology of radical-mediated protein oxidation. Biochem J 324(Pt 1):1–18

    CAS  Google Scholar 

  30. Teul J, Garcia A, Tuñón J, Martin-Ventura JL, Tarín N, Bescós LL, Egido J, Barbas C, Rupérez FJ (2011) Targeted and non-targeted metabolic time trajectory in plasma of patients after acute coronary syndrome. J Pharm Biomed Anal 56(2):343–351

    Article  CAS  Google Scholar 

Download references

Acknowledgments

Joanna Teul acknowledges her fellowship to EADS-CASA. The paper was supported by the EC, FAD project (FP-7, HEALTH F2-2008-200647), the Spanish MICINN (SAF2010/21852 and CTQ2011-23562) CAM (S2006/GEN-0247), Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III [Red RECAVA (RD06/0014/0035), and EUS2008-03565] and Fundacion Pro CNIC.

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Authors and Affiliations

  1. Cembio, Pharmacy Faculty, Campus Monteprincipe, San Pablo-CEU University, 28668, Boadilla del Monte, Spain

    Francisco J. Rupérez, Joanna Teul, Antonia Garcia & Coral Barbas

  2. Vascular Research Laboratory, IIS-Fundación Jiménez Díaz, Autónoma University, Av. Reyes Catolicos 2, 28040, Madrid, Spain

    Priscila Ramos-Mozo, Roxana Martinez-Pinna, Jesús Egido & Jose Luis Martin-Ventura

  3. Department of Pharmaceutical Analysis, Medical University in Bialystok, Kilinskiego 1, 15-089, Bialystok, Poland

    Joanna Teul

  4. Université de Toulouse, UPS Laboratoire de Synthèse et Physico-Chimie de Molécules d’Intérêt Biologique (SPCMIB), Groupe de RMN Biomédicale, 118 route de Narbonne, 31062, Toulouse cedex 9, France

    Myriam Malet-Martino, Stéphane Balayssac & Véronique Gilard

  5. Unidad de Proteómica, Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029, Madrid, Spain

    Emilio Camafeita & Juan Antonio Lopez

  6. Immunology Laboratory, IIS-Fundación Jiménez Díaz, Autónoma University, 28040, Madrid, Spain

    Carlos Pastor-Vargas

Authors
  1. Francisco J. Rupérez
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  2. Priscila Ramos-Mozo
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  3. Joanna Teul
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  4. Roxana Martinez-Pinna
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  6. Myriam Malet-Martino
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  8. Juan Antonio Lopez
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  9. Carlos Pastor-Vargas
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  10. Jesús Egido
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  11. Stéphane Balayssac
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  12. Véronique Gilard
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  13. Coral Barbas
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  14. Jose Luis Martin-Ventura
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Corresponding authors

Correspondence to Coral Barbas or Jose Luis Martin-Ventura.

Additional information

Francisco J. Rupérez, Priscila Ramos-Mozo, Coral Barbas and Jose Luis Martin-Ventura both authors and seniors contributed equally to this work.

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Rupérez, F.J., Ramos-Mozo, P., Teul, J. et al. Metabolomic study of plasma of patients with abdominal aortic aneurysm. Anal Bioanal Chem 403, 1651–1660 (2012). https://doi.org/10.1007/s00216-012-5982-y

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  • DOI: https://doi.org/10.1007/s00216-012-5982-y

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